Nephrolithiasis, also known as urolithiasis or urinary tract stone disease, is the term used to refer to the condition in which renal calculi or kidney stones occupy one or more locations in the urinary tract, e.g. major calices, minor calices, renal pelvis, ureter, etc. Renal calculi or kidney stones spontaneously develop in the ureter and can cause significant health problems, including pain, bleeding, blockage of the ureter, etc.
A number of different types of kidney stones can form in the urinary tract. Approximately 75 to 85% of all stones are calcium stones, which are typically made up of calcium oxalate and/or calcium phosphate, where the calcium phosphate is typically hydroxyapatite or brushite. Uric acid stone are stones made up of crystallized uric acid and account for approximately 5 to 8% of all observed kidney stones. Cystine stones are rare, accounting for about 1% of all observed stones. Finally, struvite stones (MgNH4PO4) account for approximately 10 to 15% of all observed stones and are typically associated with the presence of a bacterial infection.
While a significant portion of stones will spontaneously pass out of the body and may even be asymptomatic, treatment is indicated in a large number of cases. As such, a variety of different treatment protocols have been developed. Representative treatment protocols include: dietary changes, pharmacological intervention, and surgical intervention.
Surgical intervention is typically reserved for situations where the stone(s): (a) does not pass after a reasonable period of time and causes constant pain; (b) is too large to pass on its own; (c) blocks the urine flow; (d) causes ongoing urinary tract infection; (e) damages the kidney tissue or causes constant bleeding; or (e) has grown larger (as seen on follow up x-ray studies). A variety of different surgical procedures have been developed, including minimally invasive procedures such as: extracorporeal shockwave lithotripsy (ESWL); percutaneous nephrolithotomy; and ureteroscopic stone removal.
Another minimally invasive procedure that has found some use is chemolysis, in which the urinary tract is irrigated with a stone solvent, such as an organic acid solution. Chemolytic procedures provide some advantages over other treatment protocols, as the stone can be completely dissolved and removed, smaller stones can be removed along with larger ones, and stones that are difficult to access can be treated. However, known chemolytic procedures do not work effectively on all types of stones and require long treatment periods, with the patient finding the treatment protocol tedious and uncomfortable.
As such, there is continued interest in the development of new chemolytic procedures for use in the treatment of disease conditions characterized by the presence or renal calculi, where of particular interest would be the development of a protocol in which calcium containing stones, particularly calcium oxalate and calcium phosphate containing stones, are rapidly dissolved.
Relevant Literature
Patents of interest include U.S. Pat. Nos. 5,845,125 and 5,275,605. Also of interest are U.S. Pat. Nos. 4,295,464; 4,474,180; 4,790,812; 4,807,626; 4,825,851; 5,403,324; and 5,496,330. Literature references of interest include: Pfister & Dretler, Urol. Radiol. (1984) 6:138-143 and Oosterlink & Verbeeck, Acta Urologica Belgica (1994) 62:31-37.